Overview
11 DESCRIPTION Talquetamab-tgvs is a bispecific GPRC5D-directed CD3 T-cell engager. It is a humanized IgG4 proline, alanine, alanine (IgG4-PAA)-based bispecific antibody produced by Chinese hamster ovary (CHO) cells using recombinant DNA technology. Talquetamab-tgvs consists of an anti-GPRC5D heavy chain and light chain and an anti-CD3 heavy chain and light chain with two interchain disulfide...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Talquetamab-tgvs is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D) expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as healthy tissues such as epithelial cells in keratinized tissues of the skin and tongue. In vitro, talquetamab-tgvs activated T-cells caused the release of proinflammatory cytokines and resulted in the lysis of multiple myeloma cells. Talquetamab-tgvs had anti-tumor activity in mouse models of multiple myeloma. 12.
Indications
- 1 INDICATIONS AND USAGE TALVEY is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Common Doses
- 0.01 mg
- 0.06 mg
- 0.4 mg
- 0.8 mg
Dosage
2 DOSAGE AND ADMINISTRATION For subcutaneous injection. ( 2.2 ) Patients should be hospitalized for 48 hours after all doses within the step-up dosing schedule. ( 2.1 ) Administer pretreatment medications as recommended. ( 2.3 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) TALVEY Weekly Dosing Schedule ( 2.2 ) Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.
Black Box Warning
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.2 , 2.5 ) , Warnings and Precautions (5.1) ] .
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are also described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity, including ICANS [see Warnings and Precautions (5.2) ] Oral Toxicity and Weight Loss [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Cytopenias [see Warnings and Precautions (5.6) ] Skin Toxicity [see Warnings and Precautions (5.7) ] Hepatotoxicity [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS For certain cytochrome P450 (CYP) substrates, minimal changes in the substrate concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with TALVEY. Talquetamab-tgvs causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates.